Schaller, T;Märkl, B;Claus, R;Sholl, L;Hornick, JL;Giannetti, MP;Schweizer, L;Mann, M;Castells, M;
PMID: 35340030 | DOI: 10.1111/all.15293
The anti-fibrotic drug pirfenidone inhibits liver fibrosis by targeting the small oxidoreductase glutaredoxin-1
Xi, Y;Li, Y;Xu, P;Li, S;Liu, Z;Tung, HC;Cai, X;Wang, J;Huang, H;Wang, M;Xu, M;Ren, S;Li, S;Zhang, M;Lee, YJ;Huang, L;Yang, D;He, J;Huang, Z;Xie, W;
PMID: 34516906 | DOI: 10.1126/sciadv.abg9241
[Figure: see text].
International journal of surgical pathology
Mannan, R;Wang, X;Bawa, PS;Zhang, Y;Skala, SL;Chinnaiyan, AK;Dagar, A;Wang, L;Zelenka-Wang, SB;McMurry, LM;Daniel, N;Cao, X;Sangoi, AR;Gupta, S;Vaishampayan, UN;Hafez, KS;Morgan, TM;Spratt, DE;Tretiakova, MS;Argani, P;Chinnaiyan, AM;Dhanasekaran, SM;Mehra, R;
PMID: 36250542 | DOI: 10.1177/10668969221125793
Introduction: Chromophobe renal cell carcinoma (chromophobe RCC) is the third major subcategory of renal tumors after clear cell RCC and papillary RCC, accounting for approximately 5% of all RCC subtypes. Other oncocytic neoplasms seen commonly in surgical pathology practice include the eosinophilic variant of chromophobe RCC, renal oncocytoma, and low-grade oncocytic unclassified RCC. Methods: In our recent next-generation sequencing based study, we nominated a lineage-specific novel biomarker LINC01187 (long intergenic non-protein coding RNA 1187) which was found to be enriched in chromophobe RCC. Like KIT (cluster of differentiation 117; CD117), a clinically utilized chromophobe RCC related biomarker, LINC01187 is expressed in intercalated cells of the nephron. In this follow-up study, we performed KIT immunohistochemistry and LINC01187 RNA in situ hybridization (RNA-ISH) on a cohort of chromophobe RCC and other renal neoplasms, characterized the expression patterns, and quantified the expression signals of the two biomarkers in both primary and metastatic settings. Results: LINC01187, in comparison to KIT, exhibits stronger and more uniform expression within tumors while maintaining temporal and spatial consistency. LINC01187 also is devoid of intra-tumoral heterogeneous expression pattern, a phenomenon commonly noted with KIT. Conclusions: LINC01187 expression can augment the currently utilized KIT assay and help facilitate easy microscopic analyses in routine surgical pathology practice.
Virchows Arch. 2015 Aug 5.
Gastrointestinal stromal tumors (GISTs) develop from interstitial cells of Cajal (ICCs) mainly by activating mutations in the KIT or PDGFRA genes. Immunohistochemical analysis for KIT, DOG1, and PKC-θ is used for the diagnosis of GIST. Recently, ETV1 has been shown to be a lineage survival factor for ICCs and required for tumorigenesis of GIST. We investigated the diagnostic value of ETV1expression in GIST. On fresh-frozen tissue samples, RT-PCR analysis showed that ETV1 as well as KIT, DOG1, and PKC-θ are highly expressed in GISTs. On tissue microarrays containing 407 GISTs and 120 non-GIST mesenchymal tumors of GI tract, we performed RNA in situ hybridization (ISH) for ETV1 together with immunohistochemical analysis for KIT, DOG1, PKC-θ, CD133, and CD44. Overall, 387 (95 %) of GISTs were positive for ETV1, while KIT and DOG1 were positive in 381 (94 %) and 392 (96 %) cases, respectively, showing nearly identical overall sensitivity of ETV1, KIT, and DOG1 for GISTs. In addition, ETV1 expression was positively correlated with that of KIT. Notably, ETV1 was positive in 15 of 26 (58 %) KIT-negative GISTs and even positive in 2 cases of GIST negative for KIT and DOG1, whereas only 6 (5 %) non-GIST mesenchymal GI tumors expressed ETV1. We conclude that ETV1 is specifically expressed in the majority of GISTs, even in some KIT-negative cases, suggesting that ETV1 may be useful as ancillary marker in diagnostically difficult select cases of GIST.
Auguste, YSS;Ferro, A;Kahng, JA;Xavier, AM;Dixon, JR;Vrudhula, U;Nichitiu, AS;Rosado, D;Wee, TL;Pedmale, UV;Cheadle, L;
PMID: 36171430 | DOI: 10.1038/s41593-022-01170-x
Oligodendrocyte precursor cells (OPCs) give rise to myelinating oligodendrocytes throughout life, but the functions of OPCs are not limited to oligodendrogenesis. Here we show that OPCs contribute to thalamocortical presynapse elimination in the developing and adult mouse visual cortex. OPC-mediated synapse engulfment increases in response to sensory experience during neural circuit refinement. Our data suggest that OPCs may regulate synaptic connectivity in the brain independently of oligodendrogenesis.
Visualization of intestinal infections with astro- and sapovirus in mink (Neovison vison) kits by in situ hybridization
Birch, J;Leijon, M;Nielsen, S;Struve, T;Jensen, H;
| DOI: 10.1093/femsmc/xtab005
Clarification of the infection microbiology remains a challenge in the pre-weaning diarrhea (PWD) syndrome in farmed mink (Neovison vison). Duodenal, jejunal and colon sections from 36 mink kits with PWD were systematically examined by chromogen in situ hybridization targeting two incriminated viruses: mink astrovirus and mink sapovirus. Using the RNAscope 2.5 HD Duplex Assay, astrovirus and sapovirus were visualized and simultaneously demonstrated in the gut tissue. Both viruses infect enterocytes in the small intestine with a specific localization pattern; astrovirus affects the two apical thirds of the villi, whereas sapovirus generally affects the basal parts of the villi. Furthermore, we demonstrated that astrovirus in mink does not target the goblet cells. This is the first time astro- and calicivirus have been visualized in mink kit gut tissue, and these findings might be important in clarification of the impact of these viruses in the PWD syndrome.
Ma D, Wang Z, Yang L, Mu X, Wang Y, Zhao X, Li J, Lin D.
PMID: 27418132 | DOI: 10.18632/oncotarget.10560.
Although the Ventana immunohistochemistry (IHC) platform for detecting anaplastic lymphoma kinase gene (ALK) (D5F3) expression was recently approved by the US Food and Drugs Administration (FDA), fluorescence in situ hybridization (FISH) is still the "gold-standard" method recommended by the US National Comprehensive Cancer Network (NCCN) guideline for NSCLC. We evaluated 6 ALK-positive lung adenocarcinoma patients who tested Ventana IHC-positive and FISH-negative and assessed their clinical responses to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Histologic and cytologic specimens from the 6 patients were stained with Ventana anti-ALK(D5F3) rabbit monoclonal primary antibody using the OptiView™ DAB IHC detection kit and OptiView™ amplification kit on a Ventana BenchMark XT processor. In addition, they were also tested by FISH, qRT-PCR, next-generation sequencing (NGS), and RNAscope ISH analysis. All patients received crizotinib treatment and their follow-up clinical data were recorded. The objective response rate achieved with crizotinib therapy was 66.7% (4/6 partial responses and 2/6 stable disease). One patient in whom a new fusion type (EML4->EXOC6B->ALK fusion) was identified obtained a partial response. These findings indicate that patients with ALK-positive lung adenocarcinoma who test Ventana IHC-positive and FISH-negative may still respond to crizotinib therapy.
RNAScope in situ Hybridization as a Novel Technique for the Assessment of c-KIT mRNA Expression in Canine Mast Cell Tumor
Frontiers in veterinary science
De Biase, D;Prisco, F;Piegari, G;Ilsami, A;d'Aquino, I;Baldassarre, V;Zito Marino, F;Franco, R;Papparella, S;Paciello, O;
PMID: 33665215 | DOI: 10.3389/fvets.2021.591961
RNA is considered as an indicator of the dynamic genetic expression changes in a cell. RNAScope is a commercially available in situ hybridization assay for the detection of RNA in formalin-fixed paraffin-embedded tissue. In this work, we describe the use of RNAScope as a sensitive and specific method for the evaluation of c-KIT messenger RNA (mRNA) in canine mast cell tumor. We investigated the expression of c-KIT mRNA with RNAscope in 60 canine mast cell tumors (MCTs), comparing it with the histological grade and KIT immunohistochemical expression patterns. Our results showed an overall good expression of c-KIT mRNA in neoplastic cells if compared with control probes. We also observed a statistically significant correlation between histological grade and c-KIT mRNA expression. No correlations were found between KIT protein immunohistochemical distribution pattern and c-KIT mRNA expression or histological grade. Our results provide a reference basis to better understand c-KIT mRNA expression in canine MCTs and strongly encourage further studies that may provide useful information about its potential and significant role as a prognostic and predictive biological marker for canine MCTs clinical outcome.
Olson, ND;Wagner, J;Dwarshuis, N;Miga, KH;Sedlazeck, FJ;Salit, M;Zook, JM;
PMID: 37059810 | DOI: 10.1038/s41576-023-00590-0
Genetic variant calling from DNA sequencing has enabled understanding of germline variation in hundreds of thousands of humans. Sequencing technologies and variant-calling methods have advanced rapidly, routinely providing reliable variant calls in most of the human genome. We describe how advances in long reads, deep learning, de novo assembly and pangenomes have expanded access to variant calls in increasingly challenging, repetitive genomic regions, including medically relevant regions, and how new benchmark sets and benchmarking methods illuminate their strengths and limitations. Finally, we explore the possible future of more complete characterization of human genome variation in light of the recent completion of a telomere-to-telomere human genome reference assembly and human pangenomes, and we consider the innovations needed to benchmark their newly accessible repetitive regions and complex variants.
Development (Cambridge, England)
Mestres, I;Calegari, F;
PMID: 37070770 | DOI: 10.1242/dev.201574
Communication between the nervous and immune system is crucial for development, homeostasis and response to injury. Before the onset of neurogenesis, microglia populate the central nervous system, serving as resident immune cells over the course of life. Here, we describe new roles of an uncharacterized transcript upregulated by neurogenic progenitors during mouse corticogenesis: 4931414P19Rik (hereafter named P19). Overexpression of P19 cell-extrinsically inhibited neuronal migration and acted as chemoattractant of microglial cells. Interestingly, effects on neuronal migration were found to result directly from P19 secretion by neural progenitors triggering microglia accumulation within the P19 targeted area. Our findings highlight the crucial role of microglia during brain development and identify P19 as a previously unreported player in the neuro-immune crosstalk.
Neural Regeneration Research
Kang, H;Liu, Y;Li, Y;Wang, L;Zhao, Y;Yuan, R;Yang, M;Chen, Y;Zhang, H;Zhou, F;Qian, Z;
| DOI: 10.4103/1673-5374.363819
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Fomitcheva-Khartchenko, A;Kashyap, A;Geiger, T;Kaigala, GV;
PMID: 35995681 | DOI: 10.1016/j.trecan.2022.07.008
Tumor cells present complex behaviors in their interactions with other cells. This intricate behavior is driving the need to develop new tools to understand these ecosystems. The surge of spatial technologies allows evaluation of the complexity of relationships between cells present in a tumor, giving insights about tumor heterogeneity and the tumor microenvironment while providing clinically relevant metrics for tumor classification. In this review, we describe key results obtained using spatial techniques, present recent advances in methods to uncover spatially relevant biological significance, and summarize their main characteristics. We expect spatial technologies to significantly broaden our understanding of tumor biology and to generate clinically relevant tools that will ultimately impact personalized medicine.
